antivirals

• Influenza virus strains are classified by core proteins (A, B, or C), species of origin (e.g., avian, swine), and geographic site of isolation
• Amantadine & Rimantadine:

  • Mechanism: Target the M2 protein
  • Inhibit uncoating of the viral RNA of influenza-A
  • Amantadine is excreted unmetabolized in the urine, Rimantadine undergoes extensive metabolism
  • 70–90% protective in the prevention of clinical illness by influenza A
  • No cross-resistance to zanamivir and oseltamivir
• Zanamivir & Oseltamivir:

  • Neuraminidase inhibitors
  • Used for the treatment of acute uncomplicated influenza infection
  • Initiate therapy within 2 days after the onset of symptoms to reduce severity and duration of illness
  • Zanamivir has activity against both influenza A and B, administered via oral inhaler
  • Oseltamivir is an orally administered prodrug used in treatment and prophylaxis of influenza
• Agents to Treat Herpes Simplex Virus (HSV) & Varicella Zoster Virus (VZV) Infections:

  • Acyclovir, Valacyclovir, Famciclovir
  • Similar mechanisms of action and indications for clinical use
  • Well tolerated
• Acyclovir:

  • Acyclic guanosine derivative
  • Clinical activity against HSV-1, HSV-2, and VZV
  • Requires three phosphorylation steps for activation
  • Bioavailability of oral acyclovir: 15–20%
  • Used in primary genital herpes, herpes simplex encephalitis, neonatal HSV infection, and serious HSV or VZV infections
  • Resistance can develop through viral thymidine kinase or DNA polymerase
  • Well tolerated, may cause reversible renal dysfunction with intravenous infusion
• Valacyclovir:

  • L-valyl ester of acyclovir
  • Converted to acyclovir after oral administration
  • Serum levels 3-5x greater than oral acyclovir
• Famciclovir:

  • Diacetyl ester prodrug of 6-deoxypenciclovir
  • Rapidly converted to penciclovir by first-pass metabolism
  • Bioavailability of penciclovir from orally administered famciclovir is 70%
  • Used for the treatment of primary and recurrent genital herpes attacks and for chronic daily suppression
  • Well tolerated, may cause nausea, diarrhea, and headache
• Trifluridine:

  • Inhibits viral DNA synthesis
  • 1% solution effective in treating primary keratoconjunctivitis and recurrent epithelial keratitis due to HSV
• Agents to Treat Cytomegalovirus (CMV) Infections:

  • Ganciclovir
  • Requires triphosphorylation
  • Activity against CMV is up to 100 x greater than that of acyclovir
  • Can be administered intravenously, orally, or via intraocular implant
  • Clinical uses include CMV retinitis, colitis, esophagitis, and prevention in transplant recipients
  • Resistance mechanisms involve mutations in UL97 and UL54
• Cidofovir:

  • Cytosine nucleotide analog
  • Monophosphate nucleotide analog
  • Phosphorylation is independent of viral enzymes
  • Used for the treatment of CMV retinitis
  • Adverse reactions include nephrotoxicity
• Foscarnet:

  • Does not need phosphorylation
  • Available in IV formulation only
  • Used in the treatment of CMV retinitis, colitis, esophagitis, acyclovir-resistant HSV infection, and acyclovir-resistant VZV infection
  • Adverse reactions include renal insufficiency, anemia, headache, hallucinations, and seizures
• Drugs used to treat chronic hepatitis B virus infection:

  • Interferons
  • Pegylation reduces the rate of absorption following subcutaneous injection
• Thank you